Effect of petroleum ether extract of Ligulatum fiscali on preventing pulmonary fibrosis in mice through NLRP3/Caspase-1/GSDMD pathway

Objective To explore the anti-pulmonary fibrosis mechanism of Ligulatum fiscali's petroleum ether extract layer using the bleomycin (BLM)-induced mouse model of pulmonary fibrosis.Methods 32 C57BL/6 mice were selected and randomly divided into 4 groups: normal (CON) group, modeling (BLM) group, petroleum ether (BLM+PE 500 mg/kg) group, and positive control (BLM+PFD 200 mg/kg) group. To create a pulmonary fibrosis model, the normal group of mice got tracheal instillation of PBS, whereas the other groups of mice received tracheal instillation of BLM (5 mg/kg). During the second day of the modeling process, the mice in each group received oral gavage once daily for 21 consecutive days. The mice were euthanized three weeks after the modeling period, and the lung tissue was takenout to examine the pathological shape as well as the extent of inflammation and fibrosis. Western blotting was employed to identify the presence of proteins associated with pulmonary fibrosis and NLRP3 inflammasome.Results The modeling group of mice exhibited a higher amount of inflammatory cell infiltration and fibrosis changes in the lung tissue, as well as elevated levels of HYP in the lungs, compared to the control group, upregulation of fibrotic proteins α-SMA and collagen I, downregulation of E-cadherin, and increased levels of pathway proteins NLRP3, ASC, GSDMD, and Caspase-1 were observed. After undergoing treatment with petroleum ether, these symptoms were reversed and had a similar therapeutic effect as the positive control medication pirfenidone (PFD).Conclusion The petroleum ether extract of Ligulatum fiscali can ameliorate BLM-induced lung fibrosis in rats and operates through the NLRP3 inflammasome signaling pathway.